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A Phase I Study of Ganetespib +/- Bortezomib in Patients With Relapsed and/or Refractory Multiple Myeloma

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Emory University
Sponsor:
Collaborator:
Multiple Myeloma Research Consortium
Information provided by (Responsible Party):
Sagar Lonial, Emory University
ClinicalTrials.gov Identifier:
NCT01485835
First received: December 2, 2011
Last updated: October 9, 2014
Last verified: October 2014
  Purpose

The purpose of this study is to find out what effects, good and/or bad, that ganetespib and bortezomib has on you and your cancer. The investigators will determine the side effects of different dose levels of ganetespib when given alone and the effect it has on your cancer alone. The investigators will also determine the side effects of ganetespib at different dose levels when given in combination with bortezomib and the effect the combination has on your cancer. The study will measure levels of the drug in your blood and bone marrow as well.

Bortezomib is a proteasome inhibitor that is approved by the US Food and Drug Administration (FDA) that is used for the treatment of multiple myeloma. The brand name for bortezomib is Velcade®.

Ganetespib is considered "investigational" because it has not received approval from the Food and Drug Administration for general use, although it has been previously tested in humans.


Condition Intervention Phase
Multiple Myeloma
Drug: Ganetespib
Drug: Bortezomib
Drug: Dexamethasone
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Ganetespib +/- Bortezomib in Patients With Relapsed and/or Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • maximum tolerated dose (MTD) of ganetespib in combination with bortezomib and dexamethasone. [ Time Frame: 30 days after final cycle ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 15
Study Start Date: January 2012
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ganetespib + Bortezomib + Dexamethasone

Ganetespib IV Days 1, 4, 8, 11 every 3 weeks Cohort1:100 mg/m2, Cohort2:100mg/m2, Cohort3:120 mg/m2, Cohort 4:144 mg/m2,Cohort 5:173 mg/m2.

Bortezomib IV or subcutaneous Days 1, 4, 8, 11*every 3 weeks Cohort1:1.0 mg/m2, Cohort 2,3,4,5:1.3 mg/m2

Dexamethasone Oral Prior to Bortezomib Cohort1,2,3,4,5 :20 + 20 mg (Day of and following bortezomib)

Drug: Ganetespib
Standard 3+3 design to determine the maximum tolerated dose (MTD) of ganetespib when given in combination with bortezomib and dexamethasone.
Other Name: STA-9090
Drug: Bortezomib
Standard 3+3 Design to determine the maximum tolerated dose (MTD) of ganetespib when given in combination with bortezomib and dexamethasone.
Other Name: Velcade
Drug: Dexamethasone
Standard 3+3 Design to determine the maximum tolerated dose (MTD) of ganetespib when given in combination with bortezomib and dexamethasone.
Other Name: Decadron

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males or females, age 18 years or older.
  • Diagnosis of multiple myeloma (MM) and documentation of at least 2 prior therapies which must have included bortezomib and an immunomodulatory agent; there is no maximum number of prior regimens.
  • Patients with measurable disease defined as at least one of the following:

    1. Serum M-protein ≥ 0.5 g/dl (≥5 g/l)
    2. Urine M-protein ≥ 200 mg/24 h
    3. Serum free light-chain (FLC) assay: Involved FLC level ≥10 mg/dl (≥100 mg/l) and an abnormal serum free light chain ratio (<0.26 or >1.65)
    4. Measurable plasmacytoma (prior biopsy is acceptable, should be measured within 28 days of first study drug administration).
  • Subject has an Eastern Cooperative Oncology Group (ECOG) ≤ 2 OR Karnofsky ≥ 60% performance status.
  • Females of childbearing potential*: Confirmation that the subject is not pregnant must be established by a negative serum -human chorionic gonadotropin (-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. *(FCBP - A female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months).
  • Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local subject privacy regulations).
  • Voluntary written informed consent before performance of any study-related procedure not part of routine medical care with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
  • Inclusion Clinical Laboratories Criteria

    1. Absolute neutrophil count (ANC) ≥ 1,000 cells/dL (1.0 x 109/L) (Growth factors cannot be used within 7 days of first drug administration)
    2. Platelet count ≥ 75 x 109/L (platelet transfusions cannot be used within 4 days of first drug administration)
    3. Hemoglobin ≥ 8.0 g/dl
    4. Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 1.5 x upper limit of normal (ULN)
    5. Serum creatinine ≤ 1.5 x ULN OR Creatinine clearance ≥ 50 mL/min (Cockcroft-Gault calculation)
    6. Total bilirubin ≤ 1.5 x ULN
    7. Serum calcium (corrected for serum albumin) or ionized calcium ≥ lower limit of normal (LLN) (treatment of hypercalcemia is allowed and subject may enroll if hypercalcemia returns to normal with standard treatment).

Exclusion Criteria:

  • Patients who have received chemotherapy, immunomodulatory drugs (e.g., lenalidomide, thalidomide or pomalidomide), immunotherapy, radiation therapy, or any investigational drug(s) within 14 days before enrollment or who have not recovered from the side effects of the therapy to at least grade 1. Localized radiation therapy to a single site within 7 days is acceptable.
  • Prior therapy with a heat shock protein 90 (HSP90) inhibitor.
  • Daily requirement for corticosteroids (except for inhalational corticosteroids); prednisone ≤10mg/day or equivalent is permitted for other medical conditions.
  • Prior peripheral stem cell transplant within 12 weeks of the first dose of study treatment.
  • Venous access devices made of materials other than silicone.
  • History of severe allergic or hypersensitivity reactions to excipients (e.g., Polyethylene glycol [PEG] 300 and Polysorbate 80).
  • Baseline corrected QT interval (QTc) > 470 msec or previous history of QT prolongation while taking other medications.
  • Ventricular ejection fraction (Ef) < 50 % at baseline.
  • History of documented congestive heart failure (CHF), New York Heart Association class II/III/IV, with a history of dyspnea, orthopnea or edema that requires current treatment with angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, beta-blockers or diuretics. NOTE: Use of these medications for the treatment of hypertension is allowed.
  • High-risk uncontrolled arrhythmias (ventricular tachycardia, high-grade atrioventricular [AV]-block, supra-ventricular arrhythmias which are not adequately rate-controlled) that require current treatment with the following anti-arrythmic drugs: flecainide, moricizine or propafenone.
  • History of active current coronary artery disease or unstable angina.
  • Peripheral neuropathy ≥ Grade 2.
  • Treatment with chronic immunosuppressants (e.g., cyclosporine following transplantation).
  • Uncontrolled intercurrent illness including, but not limited to, human immunodeficiency virus (HIV)-positive subjects receiving combination antiretroviral therapy, severe or systemic infection, , or psychiatric illness/social situations that would limit compliance with study requirements.
  • Other medications, or severe acute/chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01485835

Contacts
Contact: Sagar Lonial, MD 404-778-5144 sloni01@emory.edu
Contact: Kenisha Barron 404-778-5144 kenisha.w.barron@emory.edu

Locations
United States, Colorado
Colorado Blood Cancer Institute Recruiting
Denver, Colorado, United States, 80218
Contact: Kenisha Barron    404-778-5144    kenisha.w.barron@emory.edu   
United States, Georgia
Emory University Hospital Midtown Recruiting
Atlanta, Georgia, United States, 30308
Contact: Kenisha Barron    404-778-5144    kenisha.w.barron@emory.edu   
Emory University Winship Cancer Institute Recruiting
Atlanta, Georgia, United States, 30322
Contact: Kenisha Barron    404-778-5144    kenisha.w.barron@emory.edu   
United States, Michigan
Barbara Ann Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Contact: Kenisha Barron    404-778-5144    kenisha.w.barron@emory.edu   
United States, Missouri
Siteman Cancer Center at Washington University Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Kenisha Barron    404-778-5144    kenisha.w.barron@emory.edu   
United States, North Carolina
Levine Cancer Institute Not yet recruiting
Charlotte, North Carolina, United States, 28204
Contact: Kenisha Barron    404-778-5144    kenisha.w.barron@emory.edu   
United States, Texas
The Center for Cancer and Blood Disorders Not yet recruiting
Fort Worth, Texas, United States, 76104
Contact: Kenisha Barron    404-778-5144    kenisha.w.barron@emory.edu   
United States, Virginia
Virginia Cancer Specialists Recruiting
Fairfax, Virginia, United States, 22031
Contact: Kenisha Barron    404-778-5144    kenisha.w.barron@emory.edu   
Sponsors and Collaborators
Emory University
Multiple Myeloma Research Consortium
Investigators
Principal Investigator: Sagar Lonial, MD Emory University Winship Cancer Institute
  More Information

No publications provided

Responsible Party: Sagar Lonial, Principal Investigator, Emory University
ClinicalTrials.gov Identifier: NCT01485835     History of Changes
Other Study ID Numbers: IRB00049962, WCI2005-11/MMRC037
Study First Received: December 2, 2011
Last Updated: October 9, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Emory University:
Multiple Myeloma
Bortezomib
Velcade
Ganetespib

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
BB 1101
Bortezomib
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents
Central Nervous System Agents
Enzyme Inhibitors
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on November 24, 2014